Triphosgene → HCID 53241943, compound
Reaction equation
[NH2:1][C:2]1([C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([O:23][CH3:24])[CH:17]=3)=[CH:13][CH:14]=2)=[O:7])[CH2:5][CH2:4][CH2:3]1.Cl[C:26](Cl)([O:28]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:12]2[N:11]=[CH:10][C:9]([N:8]3[C:6](=[O:7])[C:2]4([CH2:5][CH2:4][CH2:3]4)[NH:1][C:26]3=[O:28])=[CH:14][CH:13]=2)=[CH:17][C:18]=1[O:23][CH3:24]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 1-amino-N-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)cyclobutanecarboxamide (Intermediate 102, 60 mg) in dry dichloromethane (2 mL) TEA (0.128 mL, 0.916 mmol) was added. The reaction mixture was cooled in an ice-bath, then a solution of triphosgene (24.47 mg, 0.082 mmol) in dry dichloromethane (0.500 mL) was added dropwise. The mixture was stirred at 0° C. for 30 minutes. The reaction was maintained at 0° C. and quenched with water (10 mL). The mixture was extracted with dichloromethane (3×4 mL). The combined organic layers were dried over sodium sulphate, filtered and evaporated. The residue was purified by flash chromatography on silica gel using a 25 g SNAP column and using as eluents cyclohexane/ethylacetate from 100:0 to 50:50. This afforded the title compound (52 mg) as a white solid.
Workup
- temperatureThe reaction mixture was cooled in an ice-bath
- temperatureThe reaction was maintained at 0° C.
- customquenched with water (10 mL)
- extractionThe mixture was extracted with dichloromethane (3×4 mL)
- dry with materialThe combined organic layers were dried over sodium sulphate
- filtrationfiltered
- customevaporated
- customThe residue was purified by flash chromatography on silica gel using a 25 g SNAP column
Sources & evidence
- ORD record
- ord-b23e17f141b2499d94449edfcd372321
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09216967B2
Reaction notes
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